Executive dysfunction predicts nonresponse to fluoxetine in major depression

Background: Functional brain imaging studies of major depression have consi stently revealed hypometabolism or hypoperfusion in specific regions of the prefrontal cortex and basal ganglia. Studies of cognitive functioning in m ajor depression have suggested that some bur not all subjects exhibit cogni tive deficits that are consistent with frontal-subcortical dysfunction, alt hough the reasons for this heterogeneity are unclear. In this study, we exp lored this heterogeneity among depressed subjects by examining the relation ship between cognitive functioning and treatment outcome. Method: Subjects with major depression were administered a complete neuropsychological test battery prior to treatment with fluoxetine. Results: There were no signific ant differences between responders and nonresponders to fluoxetine in terms of age, educational achievement, number of past episodes of depression, an d estimated premorbid IQ. However, nonresponders performed significantly wo rse than responders on several pretreatment measures of executive functioni ng, after controlling for baseline group differences in depression severity , Limitations: The results are based on a small sample of primarily female subjects, resulting in low statistical power and less generalizability to s amples of male subjects with depression. Conclusions: The findings suggest that subtle prefrontal dysfunction in subjects with major depression may be predictive of pool response with particular medications. Assessment of the executive functions may play a particular role in pretreatment identificat ion of subjects likely to respond to specific medications. (C) 2000 Elsevie r Science B.V. All rights reserved.